Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 4. Side Chain Conformational Restriction Leads to ETB Selectivity

View Author Information
Metabolic Disease Research and Drug Analysis Department, Pharmaceutical Products Research Division, Abbott Laboratories, Abbott Park, Illinois 60064-6098
Cite this: J. Med. Chem. 1999, 42, 18, 3668–3678
Publication Date (Web):August 13, 1999
Copyright © 1999 American Chemical Society

    Article Views





    Other access options


    Abstract Image

    When the dialkylacetamide side chain of the ETA-selective antagonist ABT-627 is replaced with a 2,6-dialkylacetanilide, the resultant analogues show a complete reversal of receptor selectivity, preferring ETB over ETA. By optimizing the aniline substitution pattern, as well as the alkoxy group on the 2-aryl substituent, it is possible to prepare antagonists with subnanomolar affinity for ETB and with selectivities in excess of 4000-fold. A number of these compounds also show promising pharmacokinetic profiles; a useful balance of properties is found in A-192621 (38). Pharmacology studies with A-192621 serve to reveal the role of the ETB receptor in modulating blood pressure; the observed hypertensive response to persistent ETB blockade is consistent with previous postulates and indicates that ETB-selective antagonists may not be suitable as agents for long-term systemic therapy.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.


    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.


     Address correspondence to T. W. von Geldern, D-47H/AP10-LL-12E, Abbott Laboratories, 100 Abbott Park Rd; Abbott Park, IL 60064-6098. E-mail:  [email protected].

     Current address:  Amgen Inc., Thousand Oaks, CA 91320.

     Department of Drug Analysis.

    Cited By

    This article is cited by 78 publications.

    1. John-David Aubert and Lucienne Juillerat-Jeanneret . Endothelin-Receptor Antagonists beyond Pulmonary Arterial Hypertension: Cancer and Fibrosis. Journal of Medicinal Chemistry 2016, 59 (18) , 8168-8188.
    2. Takayuki Furukawa, Mamoru Tobisu, and Naoto Chatani . C–H Functionalization at Sterically Congested Positions by the Platinum-Catalyzed Borylation of Arenes. Journal of the American Chemical Society 2015, 137 (38) , 12211-12214.
    3. Joan R. Cucarull-González,, Christian Laggner, and, Thierry Langer. Influence of the Conditions in Pharmacophore Generation, Scoring, and 3D Database Search for Chemical Feature-Based Pharmacophore Models:  One Application Study of ETA- and ETB-Selective Antagonists. Journal of Chemical Information and Modeling 2006, 46 (3) , 1439-1455.
    4. Oliver F. Funk,, Viktor Kettmann,, Jan Drimal, and, Thierry Langer. Chemical Function Based Pharmacophore Generation of Endothelin-A Selective Receptor Antagonists. Journal of Medicinal Chemistry 2004, 47 (11) , 2750-2760.
    5. Hwan-Soo Jae,, Martin Winn,, Thomas W. von Geldern,, Bryan K. Sorensen,, William J. Chiou,, Bach Nguyen,, Kennan C. Marsh, and, Terry J. Opgenorth. Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 5. Highly Selective, Potent, and Orally Active ETA Antagonists. Journal of Medicinal Chemistry 2001, 44 (23) , 3978-3984.
    6. Gang Liu,, Natasha S. Kozmina,, Martin Winn,, Thomas W. von Geldern,, William J. Chiou,, Douglas B. Dixon,, Bach Nguyen,, Kennan C. Marsh, and, Terry J. Opgenorth. Design, Synthesis, and Activity of a Series of Pyrrolidine-3-carboxylic Acid-Based, Highly Specific, Orally Active ETB Antagonists Containing a Diphenylmethylamine Acetamide Side Chain. Journal of Medicinal Chemistry 1999, 42 (18) , 3679-3689.
    7. Bryan K. Becker, Jermaine G. Johnston, Carolyn M. Young, Alfredo A. Torres Rodriguez, Chunhua Jin, David M. Pollock. Endothelin B receptors impair baroreflex function and increase blood pressure variability during high salt diet. Autonomic Neuroscience 2021, 232 , 102796.
    8. Yutaka Koyama. Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders. International Journal of Molecular Sciences 2021, 22 (9) , 4333.
    9. Dingguo Zhang, Chunhua Jin, Ijeoma E. Obi, Megan K. Rhoads, Reham H. Soliman, Randee S. Sedaka, J. Miller Allan, Binli Tao, Joshua S. Speed, Jennifer S. Pollock, David M. Pollock. Loss of circadian gene Bmal1 in the collecting duct lowers blood pressure in male, but not female, mice. American Journal of Physiology-Renal Physiology 2020, 318 (3) , F710-F719.
    10. Badampudi Santosh Kumar, Gudhi Madhu, Lk Ravindranath. Synthesis, antimicrobial evaluation and in silico studies of novel 3,4-disubstituted pyrrolidinesulfonamides. Chemical Bulletin of Kazakh National University 2019, January (4) , 28-40.
    11. Takayuki Furukawa, Mamoru Tobisu, Naoto Chatani. C–H Borylation by Platinum Catalysis. Bulletin of the Chemical Society of Japan 2017, 90 (3) , 332-342.
    12. M.H. Bolli, C. Boss, J. Gatfield, M. Iglarz, A. Treiber. The Discovery of Macitentan—A Standard Medicinal Chemistry Program?. 2017, 252-283.
    13. Xing Wang, Yuxin Zhang, Qing Liu, Zhixin Ai, Yanling Zhang, Yuhong Xiang, Yanjiang Qiao. Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening. International Journal of Molecular Sciences 2016, 17 (3) , 389.
    14. Dima Abdel-Samad, Ghassan Bkaily, Sheldon Magder, Danielle Jacques. ETA and ETB receptors contribute to neuropeptide Y-induced secretion of endothelin-1 in right but not left human ventricular endocardial endothelial cells. Neuropeptides 2016, 55 , 145-153.
    15. Stephen P.H. Alexander, Helen E. Benson, Elena Faccenda, Adam J. Pawson, Joanna L. Sharman, Michael Spedding, John A. Peters, Anthony J. Harmar, . The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors. British Journal of Pharmacology 2013, 170 (8) , 1459-1581.
    16. Konstantin Alexiou, Manuel Wilbring, Klaus Matschke, Thomas Dschietzig, . Relaxin Protects Rat Lungs from Ischemia-Reperfusion Injury via Inducible NO Synthase: Role of ERK-1/2, PI3K, and Forkhead Transcription Factor FKHRL1. PLoS ONE 2013, 8 (9) , e75592.
    17. I Brochu, M Houde, L Desbiens, E Simard, F Gobeil, W Semaan, G Bkaily, P D'Orléans‐Juste. High salt‐induced hypertension in B 2 knockout mice is corrected by the ET A antagonist, A127722. British Journal of Pharmacology 2013, 170 (2) , 266-277.
    18. Wararat Kittikulsuth, Stephen W Looney, David M Pollock. Endothelin ET B receptors contribute to sex differences in blood pressure elevation in angiotensin II hypertensive rats on a high‐salt diet. Clinical and Experimental Pharmacology and Physiology 2013, 40 (6) , 362-370.
    19. Thomas Dschietzig, Anna Brecht, Cornelia Bartsch, Gert Baumann, Karl Stangl, Konstantin Alexiou. Relaxin improves TNF-α-induced endothelial dysfunction: the role of glucocorticoid receptor and phosphatidylinositol 3-kinase signalling. Cardiovascular Research 2012, 95 (1) , 97-107.
    20. SPH Alexander, A Mathie, JA Peters. G PROTEIN‐COUPLED RECEPTORS. British Journal of Pharmacology 2011, 164 (s1)
    21. Masashi Tawa, Taiki Fukumoto, Mamoru Ohkita, Naoto Yamashita, Ayman Geddawy, Takeshi Imamura, Kazuhide Ayajiki, Tomio Okamura, Yasuo Matsumura. Effects of exogenous big endothelin-1 on postischemic cardiac dysfunction and norepinephrine overflow in rat hearts. Hypertension Research 2011, 34 (2) , 218-224.
    22. Erika I. Boesen, David M. Pollock. Cooperative role of ET A and ET B receptors in mediating the diuretic response to intramedullary hyperosmotic NaCl infusion. American Journal of Physiology-Renal Physiology 2010, 299 (6) , F1424-F1432.
    23. Erika I. Boesen, Jennifer S. Pollock, David M. Pollock. Contrasting effects of intervention with ET A and ET B receptor antagonists in hypertension induced by angiotensin II and high-salt dietThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.. Canadian Journal of Physiology and Pharmacology 2010, 88 (8) , 802-807.
    24. N.F. Kelland, R.E. Kuc, D.L. McLean, A. Azfer, A.J. Bagnall, G.A. Gray, F.H. Gulliver-Sloan, J.J. Maguire, A.P. Davenport, Y.V. Kotelevtsev, D.J. Webb. Endothelial cell-specific ET B receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1This article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.. Canadian Journal of Physiology and Pharmacology 2010, 88 (6) , 644-651.
    25. Kento Kitada, Nozomi Yui, Chika Matsumoto, Tatsuhiko Mori, Mamoru Ohkita, Yasuo Matsumura. Inhibition of Endothelin ET B Receptor System Aggravates Neointimal Hyperplasia after Balloon Injury of Rat Carotid Artery. Journal of Pharmacology and Experimental Therapeutics 2009, 331 (3) , 998-1004.
    26. . 7TM RECEPTORS. British Journal of Pharmacology 2009
    27. . Endothelin. British Journal of Pharmacology 2009, S42-S43.
    28. Hong-Qiang Feng, Nate D. Weymouth, Don C. Rockey. Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease. American Journal of Physiology-Gastrointestinal and Liver Physiology 2009, 297 (1) , G27-G33.
    29. Michael J. Palmer. 5 Endothelin Receptor Antagonists: Status and Learning 20 Years On. 2009, 203-237.
    30. Thomas Dschietzig, Kosta Alexiou, Christoph Richter, Martin Bobzin, Gert Baumann, Karl Stangl, Friedrich Brunner. ENDOTOXIN CAUSES PULMONARY HYPERTENSION BY UPREGULATING SMOOTH MUSCLE ENDOTHELIN TYPE-B RECEPTORS. Shock 2008, 30 (2) , 189-196.
    31. Michael C. Myers, Parag P. Shah, Mary Pat Beavers, Andrew D. Napper, Scott L. Diamond, Amos B. Smith, Donna M. Huryn. Design, synthesis, and evaluation of inhibitors of cathepsin L: Exploiting a unique thiocarbazate chemotype. Bioorganic & Medicinal Chemistry Letters 2008, 18 (12) , 3646-3651.
    32. Jean-Claude Honoré, Émilie Carrier, Marie-Hélène Fecteau, Carlos R. Tirapelli, Ghassan Bkaily, Pedro D’Orleans-Juste. Nonselective ET A /ET B -receptor blockade increases systemic blood pressure of Bio 14.6 cardiomyopathic hamstersThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.. Canadian Journal of Physiology and Pharmacology 2008, 86 (6) , 394-401.
    33. N S Kirkby, P W F Hadoke, A J Bagnall, D J Webb. The endothelin system as a therapeutic target in cardiovascular disease: great expectations or bleak house?. British Journal of Pharmacology 2008, 153 (6) , 1105-1119.
    34. Michael C. Myers, Parag P. Shah, Scott L. Diamond, Donna M. Huryn, Amos B. Smith. Identification and synthesis of a unique thiocarbazate cathepsin L inhibitor. Bioorganic & Medicinal Chemistry Letters 2008, 18 (1) , 210-214.
    35. J. C. Sullivan, T. T. Goodchild, Z. Cai, D. M. Pollock, J. S. Pollock. Endothelin A (ET A ) and ET B receptor‐mediated regulation of nitric oxide synthase 1 (NOS1) and NOS3 isoforms in the renal inner medulla. Acta Physiologica 2007, 191 (4) , 329-336.
    36. Janet J. Maguire, Anthony Davenport. ET-B Endothelin Receptor. 2007, 1-7.
    37. Shane Perrine. A192621. 2007, 1-3.
    38. Juliana Geremias Chichorro, Aleksander Roberto Zampronio, Gloria Emilia Petto Souza, Giles Alexander Rae. Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in rats: Reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs. Pain 2006, 123 (1) , 64-74.
    39. Sophie Motte, Kathleen McEntee, Robert Naeije. Endothelin receptor antagonists. Pharmacology & Therapeutics 2006, 110 (3) , 386-414.
    40. Ryan M. Fryer, Pamela A. Rakestraw, Patricia N. Banfor, Bryan F. Cox, Terry J. Opgenorth, Glenn A. Reinhart. Blood pressure regulation by ET A and ET B receptors in conscious, telemetry-instrumented mice and role of ET A in hypertension produced by selective ET B blockade. American Journal of Physiology-Heart and Circulatory Physiology 2006, 290 (6) , H2554-H2559.
    41. S P H Alexander, A Mathie, J A Peters. Endothelin. British Journal of Pharmacology 2006, 152 , S33-S34.
    42. Edward W Inscho, John D Imig, Anthony K Cook, David M Pollock. ET A and ET B receptors differentially modulate afferent and efferent arteriolar responses to endothelin. British Journal of Pharmacology 2005, 146 (7) , 1019-1026.
    43. Abraham Koshy, Andrea De Gottardi, Monika Ledermann, Hans Saegesser, Sidney G. Shaw, Arthur Zimmermann, Jürg Reichen. Endothelial nitric oxide synthase is not essential for the development of fibrosis and portal hypertension in bile duct ligated mice. Liver International 2005, 25 (5) , 1044-1052.
    44. Gerard D’Angelo, Jennifer S. Pollock, David M. Pollock. Endogenous endothelin attenuates the pressor response to acute environmental stress via the ET A receptor. American Journal of Physiology-Heart and Circulatory Physiology 2005, 288 (4) , H1829-H1835.
    45. Satoshi Yamamoto, Noriko Matsumoto, Mitsuo Kanazawa, Marie Fujita, Masanori Takaoka, Cheryl E. Gariepy, Masashi Yanagisawa, Yasuo Matsumura. Different Contributions of Endothelin-A and Endothelin-B Receptors in Postischemic Cardiac Dysfunction and Norepinephrine Overflow in Rat Hearts. Circulation 2005, 111 (3) , 302-309.
    46. Jan Michael Williams, Jennifer S. Pollock, David M. Pollock. Arterial Pressure Response to the Antioxidant Tempol and ET B Receptor Blockade in Rats on a High-Salt Diet. Hypertension 2004, 44 (5) , 770-775.
    47. Anna P Piovezan, Pedro D'Orléans‐Juste, Monica Frighetto, Glória E P Souza, Maria G M O Henriques, Giles A Rae. Endothelins contribute towards nociception induced by antigen in ovalbumin‐sensitised mice. British Journal of Pharmacology 2004, 141 (4) , 755-763.
    48. Theresa A. Guise, Khalid S. Mohammad. Endothelins in Bone Cancer Metastases. 2004, 197-212.
    49. C.M Peters, T.H Lindsay, J.D Pomonis, N.M Luger, J.R Ghilardi, M.A Sevcik, P.W Mantyh. Endothelin and the tumorigenic component of bone cancer pain. Neuroscience 2004, 126 (4) , 1043-1052.
    50. Khalid S. Mohammad, Theresa A. Guise. Mechanisms of Osteoblastic Metastases: Role of Endothelin-1. Clinical Orthopaedics and Related Research 2003, 415 , S67-S74.
    51. Juan Juan Yin, Khalid S. Mohammad, Sanna M. Käkönen, Stephen Harris, J. Ruth Wu-Wong, Jerry L. Wessale, Robert J. Padley, I. Ross Garrett, John M. Chirgwin, Theresa A. Guise. A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proceedings of the National Academy of Sciences 2003, 100 (19) , 10954-10959.
    52. Monika Buchholz, Hans‐Ulrich Reißig. Enantioselective Synthesis of the Pyrrolidine Core of Endothelin Antagonist ABT‐627 (Atrasentan) via 1,2‐Oxazines. European Journal of Organic Chemistry 2003, 2003 (18) , 3524-3533.
    53. Ivanka Vassileva, Christy Mountain, David M. Pollock. Functional Role of ET B Receptors in the Renal Medulla. Hypertension 2003, 41 (6) , 1359-1363.
    54. Traci A. Taylor, Cheryl E. Gariepy, David M. Pollock, Jennifer S. Pollock. Unique endothelin receptor binding in kidneys of ET B receptor deficient rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2003, 284 (3) , R674-R681.
    55. Theresa A. Guise, Juan Juan Yin, Khalid S. Mohammad. Role of endothelin-1 in osteoblastic bone metastases. Cancer 2003, 97 (S3) , 779-784.
    56. Thomas Dschietzig, Cornelia Bartsch, Christoph Richter, Michael Laule, Gert Baumann, Karl Stangl. Relaxin, a Pregnancy Hormone, Is a Functional Endothelin-1 Antagonist. Circulation Research 2003, 92 (1) , 32-40.
    57. Adviye Ergul. Development of endothelin receptor antagonists as potential therapeutic agents. Expert Opinion on Therapeutic Patents 2003, 13 (1) , 33-44.
    58. Glenn A. Reinhart, Lee C. Preusser, Sandra E. Burke, Jerry L. Wessale, Craig D. Wegner, Terry J. Opgenorth, Bryan F. Cox. Hypertension induced by blockade of ET B receptors in conscious nonhuman primates: role of ET A receptors. American Journal of Physiology-Heart and Circulatory Physiology 2002, 283 (4) , H1555-H1561.
    59. Fumiko Konishi, Yuka Okada, Masanori Takaoka, Cheryl E Gariepy, Masashi Yanagisawa, Yasuo Matsumura. Role of endothelin ETB receptors in the renal hemodynamic and excretory responses to big endothelin-1. European Journal of Pharmacology 2002, 451 (2) , 177-184.
    60. Guido Eibl, Bence Forgacs, Hubert G. Hotz, Heinz J. Buhr, Thomas Foitzik. Endothelin A but Not Endothelin B Receptor Blockade Reduces Capillary Permeability in Severe Experimental Pancreatitis. Pancreas 2002, 25 (2) , e15-e20.
    61. Susan Wai Sum Leung, Su Lin Lim, Catherine Cheuk Ying Pang, Ricky Ying Keung Man. Use of A-192621 and IRL-2500 to Unmask the Mesenteric and Renal Vasodilator Role of Endothelin ETB Receptors. Journal of Cardiovascular Pharmacology 2002, 39 (4) , 533-543.
    62. Ellen W. Baxter, Allen B. Reitz. Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents. 2002, 1-714.
    63. Melvin G. Perry, Mariela M. Molero, Ararat D. Giulumian, Prasad V. G. Katakam, Jennifer S. Pollock, David M. Pollock, Leslie C. Fuchs. ET B receptor-deficient rats exhibit reduced contraction to ET-1 despite an increase in ET A receptors. American Journal of Physiology-Heart and Circulatory Physiology 2001, 281 (6) , H2680-H2686.
    64. Hui Xu, Gregory D. Fink, James J. Galligan. Endothelin-1–Induced Elevation in Blood Pressure Is Independent of Increases in Sympathetic Nerve Activity in Normotensive Rats. Journal of Cardiovascular Pharmacology 2001, 38 (5) , 784-795.
    65. David M. Pollock, Jennifer S. Pollock. Evidence for endothelin involvement in the response to high salt. American Journal of Physiology-Renal Physiology 2001, 281 (1) , F144-F150.
    66. Kevin M. Madsen, Mark G. Neerhof, Jerry L. Wessale, Larry G. Thaete,. Influence of ETB Receptor Antagonism on Pregnancy Outcome in Rats. Journal of the Society for Gynecologic Investigation 2001, 8 (4) , 239-244.
    67. DAVID M. POLLOCK. Contrasting pharmacological ET B receptor blockade with genetic ET B deficiency in renal responses to big ET-1. Physiological Genomics 2001, 6 (1) , 39-43.
    68. Karl Stangl, Michael Laule, Christoph Richter, Verena Stangl, Jonas Koch, Öndar Göktas, Gert Baumann, Thomas Dschietzig. Pulmonary adrenomedullin counteracts deterioration of coronary flow and myocardial performance evoked by pulmonary endothelins in experimental acute respiratory distress syndrome. Critical Care Medicine 2001, 29 (5) , 1027-1032.
    69. Yasuhiko Kanda, Yasuyuki Kawanishi, Katsuo Oda, Teruo Sakata, Shin-ichi Mihara, Kenji Asakura, Toshiyuki Kanemasa, Mitsuyoshi Ninomiya, Masafumi Fujimoto, Toshiro Konoike. Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists. Bioorganic & Medicinal Chemistry 2001, 9 (4) , 897-907.
    70. J.W Kiel. Endothelin Modulation of Choroidal Blood Flow in the Rabbit. Experimental Eye Research 2000, 71 (6) , 543-550.
    71. Chengde Wu. Recent discovery and development of endothelin receptor antagonists. Expert Opinion on Therapeutic Patents 2000, 10 (11) , 1653-1668.
    72. Yasuhiko Kanda, Tadashi Takahashi, Yoshitaka Araki, Toshiro Konoike, Shin-ichi Mihara, Masafumi Fujimoto. Discovery and synthesis of a potent sulfonamide ETB selective antagonist. Bioorganic & Medicinal Chemistry Letters 2000, 10 (16) , 1875-1878.
    73. Paul Mulder, Houssaine Boujedaini, Vincent Richard, Genevieve Derumeaux, Jean Paul Henry, Sylvanie Renet, Jerry Wessale, Terry Opgenorth, Christian Thuillez. Selective Endothelin-A Versus Combined Endothelin-A/Endothelin-B Receptor Blockade in Rat Chronic Heart Failure. Circulation 2000, 102 (5) , 491-493.
    74. Y. Dai, D. M. Pollock, R. L. Lewis, C. J. Wingard, V. S. Stopper, T. M. Mills. Receptor-specific influence of endothelin-1 in the erectile response of the rat. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2000, 279 (1) , R25-R30.
    75. David M. Pollock, Graham H. Allcock, Arthi Krishnan, Brian D. Dayton, Jennifer S. Pollock. Upregulation of endothelin B receptors in kidneys of DOCA-salt hypertensive rats. American Journal of Physiology-Renal Physiology 2000, 278 (2) , F279-F286.
    76. Michael F Jarvis, Jerry L Wessale, Chang Z Zhu, James J Lynch, Brian D Dayton, Samuel V Calzadilla, Robert J Padley, Terry J Opgenorth, Elizabeth A Kowaluk. ABT-627, an endothelin ETA receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain. European Journal of Pharmacology 2000, 388 (1) , 29-35.
    77. Gang Liu. Chapter 8. Recent advances in endothelin antagonism. 2000, 73-82.
    78. A. P. Davenport, J. J. Maguire. Endothelin. , 295-329.